Summary of work: The Department of Nuclear Medicine, in conjunction with the National Cancer Institute and the Department of Radiology, performs clinical research in the use of imaging in oncology, and in several other disease processes. In particular, NCI is studying the use of Positron Emission Tomographic (PET) images, in conjunction with CT and MR images, to evaluate the effects of therapy on tumors. Several therapeutic agents are being studied, among them various anti-angiogenesis therapies. The PET scanners are used to measure glucose metabolism, blood flow and blood volume in tumors over the course of therapy. CT scans are used to determine tumor morphology, and MR imaging is used to determine both morphology and parameters related to tumor perfusion. This research is geared toward developing, implementing and testing methods to better quantify the data obtained from the images, and to determine if these methods are efficacious for the monitoring of tumor therapy. These methods involve both determination of tumor morphology, as well as the optimal determination of functional parameters such as blood flow, metabolism, and blood volume. The overall goal is the development of a clinically useful methodology for determining tumor response to therapy at an earlier phase of therapy than is currently possible. Such a methodology could permit optimal adjustment of the course of therapy while the therapy was still proceeding, potentially improving both tumor response and patient morbidity. Several areas of investigation are being pursued toward achieving this goal. Some of the principal ones are listed below. 1. Assessment of the physiologic models employed for blood flow measurement, using O-15 water. Several models are being analyzed, especially in regards to their utility in producing functional flow images. In addition, the results of these PET flow models are being compared to similar data obtained from Gd-DTPA dynamic MR images. The variability and reproducibility of each of the methods is also being determined, using replicate measurements. Current work is focussed on better models to account for tumor heterogeneity. 2. Methods for making accurate, quantitative measurements of FDG metabolism. Several schemes are being explored to compare the simple "SUV" (standardized uptake value) method with Patlak analysis, and to explore methods to simplfy the kinetic model method while retaining accuracy. Initial results of this work have been recently accepted for publication in the European Journal of Nuclear Medicine, and in the Journal of Nuclear medicine. In addition, a method for making parametric images of glucose metabolism in tumors has been developed. Initial results were described in an oral presentation at the Society of Nuclear Medicine. 3. The above methods, combined with partial volume corrections from CT, and factor analysis/principal components analysis will be employed to make objective assessments of the various physiologic parameters (e.g. FDG "uptake"), and ROC analysis used to determine which of these quantitative indices are best for detecting disease, and to determine if such quantitative measures are better than subjective visual assessment. These studies will be performed in conjunction with Dr. I. Buvat at INSERM in Paris. A new simplified Patlak Analysis method was developed. Initial results were presented orally at the June 2003 Society of Nuclear Medicine meeting, and a manuscript is currently in review with the Journal of Nuclear Medicine. In addition, a manuscript was published in the Journal of Molecular Imaging and Biology describing the blood flow and metabolism measurements as applied to prostate cancer.